Journal of Pathology and Translational Medicine

Original Articles

The Expression Rate and Pattern of HBcAg and HBsAg in the Hepatocytes According to the Histologic Activity of Cirrhosis.: Yoon Mi Jeen, Chanil Park; Korean J Pathol. 1995;29(5):669-677.

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Abstract: Since the discovery of hepatitis B virus as one of the causes of hepatitis, liver and hepatocellular carcinoma, many hepatitis B viral markers that appear in infected individuals have been discovered and many efforts to understand the relationship between the emergence of viral markers and the progression of hepatitis have been performed. Gudat (1975) compared the expression of HBcAg and HBsAg in various conditions and stages of hepatitis but the pattern of expression of viral markers and its significance have not been understood. Recently it was found by mierocytotoxicity assay that HBcAg might be the target of T lymphocytes. This study attempted to identify any correlation of the tissue expression rate and pattern of HBcAg and HBsAg with the histologic activity of 46 cases of liver cirrhosis using immunohistochemical staining. The expression rate and pattern of HBcAg and HBsAg in relation to the nodular size and positivity of serum HBeAg were also compared. The results were as follows; 1) The expression rate of HBcAg in the liver was 41.3% (19/46). and that of HBsAg was 67.4% (31/46). 2) The histologic activity of liver cirrhosis appeared to be correlated with the expression of HBcAg, especially cytoplasmic HBcAg. 3) The positivity of serum HBeAg was significantly higher in active liver cirrhosis. 4) There was no relationship between the tissue expression of HBsAg and the histologic activity of liver cirrhosis. relationship existed between the nodular size and expression rate and pattern of HBcAg and HBsAg. This study suggests that the tissue HBcAg, especially the cytoplasmic HBcAg is the most likely factor determining the histologic activity of liver cirrhosis, and that the cytoplasmic HBcAg may be the ultimate cause and target of most host immune response.

The Tissue Expression of HBsAg and HBcAg in Hepatocellular Carcinoma and Peritumoral Liver.: Jee Young Han, Woo Hee Jung, Chae Yoon Chon, Chan Il Park; Korean J Pathol. 1993;27(4):371-378.

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Abstract PDF: To evaluate the tissue expression rate and pattenr of HBsAg and HBcAg in tumors and peritumoral livers, an immunohistochemical study was undertaken on 47 surgically resected hepatocellular carcinomas(HCCs). The results are as follows. 1. Patient's sera were positive for HBsAg in 40 cases(85.1%). In the remaining 7 cases, the tumor and peritumoral liver expressed neither HBcAg nor HbSaG, suggesting that they were caused by other etiologies than hepatitis B virus. 2. The peritumoral liver had HBsAg and HBcAg in 95.0% and 27.5% among the 40 cases, respectively. But the tumor expressed HBsAg in 50.0% and HBcAg in none. 3. The expression of HBsAg within the tumor and both HBsAg and HBcAg in the peritumoral liver tended to be more frequent in the pretreated cases before surgery. 4. Edmondson-Steiner grade IV tumors revealed a lower expression rate of HBsAg than the low grade tumors(p<0.05). Incases with cirrhosis at peritumoral tissues, HBcAg was less frequently found than in those without cirrhosis. The majority of tissue HBsAg and HBcAg was represented as groups of positive cells. These results suggest that, during the development and progression of HCCs, the HBcAg containing cells are repeatedly removed and the HBcAg negative cells are selected, because cellular expression of HBcAg is the target of host immune response.

Biologic Significance of Hepatocyte Hepatitis B Core Antigen Expression in Chronic Hepatitis B Virus Infection II.: Hye Kyung Lee, Kwang Min Lee, Dong Kyu Chung; Korean J Pathol. 1992;26(4):355-359.

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Abstract PDF: Routine use of commercially available antisera against hepatitis B core antigen(HBcAg) has permitted a reevaluation of the histochemical distribution of the antigen in liver tissue. HBcAg, classically described almost exclusively in the nucleus, was found with a very high frequency in the cytoplasm of liver cells as well. To elucidate the biologic significance of HBcAg expression and its relation to the natural course of hepatitis B virus(HBV) infection, the patterns of activity in 33 needle liver biopsies of HBsAg carriers were analysed. A good correlation of liver HBcAg with disease activity was demonstrated. HBcAg was present in the hepatocyte nuclei(nHBcAg) or cytoplasm(cHBcAg), or in both(mixed). Pure nHBcAg was seen mainly in non-aggressive reactive liver tissue and cHBcAg was predominantly associated with chronic active hepatitis(95%). The results suggest that expression of HBcAg correlates with the liver pathology and the possibility of HBcAg to be an immunological target for T cell mediated hepatocyte damage.

Expression pattern of Hepatitis B Viral Core Antigen (HBcAg) and Surface Antigen (HBsAg) in Liver of the Inactive HBsAg Carriers.: Hee Jeong Ahn, Kyoung Ho Kim, Young Nyun Park, Ho Guen Kim, Chan Il Park; Korean J Pathol. 1990;24(2):120-127.

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Abstract PDF: To understand better the complex natural course of HBV infection, the expression patterns of HBcAg and HBsAg in the liver of 51 inactive serum HBsAg carriers (24 CPH and 27 NPD) were studied by immunohistochemical methods. The inactive serum HBsAg carriers were devided into 3 groups by the following expression patterns of serum HBeAg/anti-HBe status and tissue HBcAg and HBsAg. Pattern A (18 cases) : HBeAg+, cHBcAg+ (94.4%), mHBsAg+ (61.1%), pATTERN B (14 cases) : anti-HBe+, nHBcAg+, cHBsAg+, Pattern C (19 cases) : anti-HBe+, HBcAg-, cHBsAg+ (89.5%). There were no significant differences between CPH and NPD, lthough the core free pattern was more common in the latter. The cHBcAg was expressed in 17 of 18 (94.4%) HBeAg seropositive cases but only one of 33 cases with serum anti-HBe, suggesting that the cHBcAg is intimately related to HBeAg. Since the inactive HBsAg carriers also expressed cHBcAg and/or mHBsAg, the necro-inflammatory activity of HBV infected liver is assumed to depend on the host immune response rather than their presence alone

Biologic Significance of Hepatocyte Hepatitis B Core Antigen Expression in Chronic Hepatitis B Virus Infection.: Hye Kung Lee, Sang Ho Kim; Korean J Pathol. 1989;23(3):287-291.

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Abstract PDF: To elucidate the biologic significause of hepatocyte B core antigen (HBcAg) expression and its relation to the natural course of hepatitis B virus (HBV) infection, we tried to correlate the patterns of HBcAg with the HBV replication state and with disease activity in 40 needle biopsies performed on hepatitis B surface antigen (HBsAg) carriers aged from 15 to 46 years. In 32 of 40 cases, HBcAg was present in the hepatocyte nucleus (nHBcAg), in the cytoplams (cHBcAg) or in both (mixed). Pure nHBcAg was seen only in minimal hepatitis, but a diffuse pattern of expression of cytoplasmic HBcAg and mixed cytoplasmic and nuclear expression of HBcAg were seen in active hepatitis. There was also a good correlation between liver HBcAg and serum HBeAg.
Case
s in which HBcAg expression were observed were positive for serum HBeAg (81%) and the cases negative for HBcAg were all positive for serum anti-HBe.

Occurrence of Hepatitis B-Virus Antigens in a Consecutive Material of 112 Liver Biopsies.: S P Kim, C H Kim, S S Lee, C H Chung; Korean J Pathol. 1988;22(4):404-414.

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Abstract PDF: The frequency and occurrence of HBsAg and HBcAg in 112 consecutive, HBsAg sero-positive, liver biopsies were determined using immunoperxidase staining, HBsAg and HBcAg were demonstrated in 35 (31.3%) and 71 (63.4%) biopsies, respectively. HBsAg in liver was found in the cytoplasm as diffuse granules, mostly in the form of cytoplasmic inclusions. There was also perinuclear and membranous patterns. HBcAg in liver was found mostly in the cytoplasm and occasionally confined to the nucleus. The highest correspondence between HBsAg positivity in serum and liver was found in cases with normal histology morphology (80%). The frequency of HBs and HBcAg in liver in chronic liver disease was 23.1~50% and 36.4~69.2%. According to the variable expression pattern of HBs & c Ags in liver cells, 47 cases (42%) showed only HBcAg in liver. Twenty-nine cases (25.6%) failed to demonstrate any HBV Ags in liver and 24 cases showed boty antigens in liver. No correlation was found between liver disease groups and HBV Ag expression patterns. However, 11 cases (9.8%) showed only HBsAg in liver; predominant HBsAg pattern was observed in 80% of "normal histology group". 73.2% of HBsAg positive patients had anti-HBc in serum and 57.7% of them had HBeAg. 70.3% of anti-HBc positive and 70.7% of HBeAg sero-positive patients had HBcAg in liver cells. These findings strongly suggest that the presence of HBcAg. Serum HBeAg and anti-HBc can be used as a reliable indicator of active viral replication. The overall results further suggest an interplay of both hepatitis B virus and host immune response in the development and pathogenesis of hepatitis, including different degrees of accumulation of HBsAg and HBcAg in the liver and the various histological types of hepatitis.

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